Previous studies have demonstrated that pretreatment with platelet inhibitory doses of aspirin (ASA) augments epicardial collateral flow by greater than 50% four hours after ligation of the left anterior descending coronary artery (LAD) in dogs. To determine whether this effect is sufficient to reduce the size of subsequent myocardial infarction, we administered ASA to 17 dogs and saline to 16 control dogs prior to LAD occlusion. After 3 days, animals were sacrificed. In vitro perfusion of the aortic root with Evan's blue and of the LAD distal to occlusion identified the unstained myocardium as the region at risk of infarction. Further staining of this region with tetrazolium identified viable from infarcted tissue. ASA treated dogs showed no difference from controls in %LV at risk, in % infarct/LV, and in % infarct/risk region. Thus, despite the potentially beneficial increase in epicardial collateral flow produced by ASA pre-treatment, we found that ASA failed to significantly reduce infarct size.